title: Preventive effect of t,t-conjugated linoleic acid on 12-O-tetradecanoylphorbol-13-acetate-induced inhibition of gap junctional intercellular communication in human mammary epithelial MCF-10A cells.
abstract: The anti-tumor promotional effects of t9,t11-conjugated linoleic acid (t9,t11-CLA) and t10,t12-CLA were evaluated on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inhibition of gap junctional intercellular communication (GJIC) in the human mammary epithelial cell line MCF-10A. The results were compared to those obtained from c9,t11-CLA, which is a more effective anti-tumor promoter on TPA-induced GJIC inhibition in MCF-10A cells than t10,c12-CLA. Cells were treated with 20 μM t9,t11-CLA, t10,t12-CLA, or c9,t11-CLA for 24 h followed by 60 nM TPA for 1 h. Both t9,t11-CLA and t10,t12-CLA equally protected MCF-10A cells from TPA-induced inhibition of GJIC with inferior efficacy to c9,t11-CLA.The protection was due to the ameliorated phosphorylation of connexin43 via suppression of extracellular signal-regulated kinases (ERK1/2) activation. Suppression of TPA-induced reactive oxygen species (ROS) generation by t9,t11-CLA and t10,t12-CLA was less effective, relative to c9,t11-CLA. The results suggest that the anti-promotional activities of t9,t11-CLA and t10,t12-CLA are equal but less potent than c9,t11-CLA in TPA-treated MCF-10A cells. The activity might be mediated by the attenuation of ROS production in MCF-10A cells by preventing the downregulation of GJIC during the cancer promotion stage.
authors.affiliation: Division of Applied Life Science (BK21 Program), Graduate School, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Md Abdur
authors.initials: MA
authors.lastname: Rakib
authors.forename: Young S
authors.initials: YS
authors.lastname: Kim
authors.forename: Wook J
authors.initials: WJ
authors.lastname: Jang
authors.forename: Joung S
authors.initials: JS
authors.lastname: Jang
authors.forename: Seok J
authors.initials: SJ
authors.lastname: Kang
authors.forename: Yeong L
authors.initials: YL
authors.lastname: Ha
mesh_terms: D002460:Cell Line; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D019787:Linoleic Acid; D013755:Tetradecanoylphorbol Acetate